Device

ABSTRACT

There is described an air amplifying system comprising an amplifying fluid jet provided with a fluid inlet and a fluid outlet, the fluid outlet being linked to an outlet nozzle via an amplifying passage, the amplifying passage also being linked to a powder chamber, said chamber being adapted for non-laminar powder flow, such that fluid travelling from the fluid outlet of the jet draws extraneous air and aerosolised powder through the powder chamber so that the extraneous air and aerosolised powder mix with the amplifying fluid in the amplifying passage and the amplified mixture exits through the outlet nozzle. There is also described a powder delivery device comprising such an air amplifying system and a method of treatment related thereto.

[0001] This invention relates to a novel air amplifying system and anovel powder delivery device comprising such a system, for example, amedicament delivery device, such as an inhaler.

[0002] In particular the invention provides a novel form of dry powderinhaler and a method of delivering a powder using such an inhaler.

[0003] Conventional powder delivery devices, such as dry powder inhalers(DPIs), deliver a powder dosage by the aerosolisation of the powder, theaerosolisation being largely driven by the inhalation of the patient.One disadvantage with these conventional DPIs is that the extent ofaerosolisation, and therefore the consistency of the dosage delivered,is dependent upon, inter alia, the inspiratory flow of the patient, thenature of the air passage and the nature of the formulation.

[0004] Attempts have been made to improve on conventional DPIs by using,for example, an air jet directed at or across a powder. However, suchsystems suffer from a number of disadvantages in that, inter alia,

[0005] (i) A powder container may be difficult to completely empty,giving rise to problems with dosage consistency and with efficiency ofdelivery. There may also be a lack of any real element of control of theair stream.

[0006] (ii) There is no amplification, i.e., the volume of air enteringthe device is the same as the volume of air leaving the device; whichnay limit the efficiency of powder aerosolisation.

[0007] (iii) Air flowing across the powder due to the inhalation of apatient can only lift the powder into the airstream and therefore doesnot efficiently aerosolise the powder.

[0008] Conventional metered dose inhalers (MDIs) attempt to address thisproblem by the use of a volatile propellant to create a pressuresufficient to aerosolise the medicament. However, one disadvantage ofMDIs is that the combination of a volatile propellant to create apressure sufficient to aerosolise the medicament, and a solubilisedmedicament can give rise to blocking or clogging of the valve throughwhich the aerosolised medicament is emitted. In addition MDIs aredisadvantageous in that, inter alia, they lack the ability toco-ordinate actuation with inhalation, and suffer from high drugimpaction in the oropharynx, although breath actuation systems mayovercome these issues to a certain extent.

[0009] U.S. Pat. No. 6,158,675 to Nathaniel Hughes, describes amicroatomising device which uses a vortex accumulation resonant chamberthe use of which creates a vacuum to enable outside entrainment air tobe drawn into the device, lowering the speed of delivery of themedicament particles to the lung.

[0010] U.S. Pat. No. 4,114,615 to Draco AB, describes an aerosolinhalation device which, inter alia, activates a liquid propellant. Inuse, the propellant flows past a capillary arranged in a medicamentcontainer. The specification describes, at column 3, lines 59 to 63,that when the propellant passes across the top of the capillary, themedicament is drawn from the chamber.

[0011] U.S. Pat. No. 5,657,794 to Inhale Therapeutics Inc. describes adry powder inhaler which is provided with a curved section of a passagewhich creates a Venturi effect to empty a powder containing receptacle.A feed tube is positioned so that an inlet end of the tube enters thereceptacle and a high velocity gas stream is released which creates a‘low pressure region’ at the outlet end of the feed tube. This lowpressure region that is created acts to draw fluidisation air into thereceptacle, to fluidise and/or aerosolise the powder and extract thepowder through the feed tube and into the high velocity gas stream.Although the device addresses the problem of more complete emptying ofthe powder receptacle by the utilisation of a walled passage whichcommunicates and co-operates with a depression in the powder receptacleto create a Venturi effect, such a device may, inter alia, havelimitations in efficiency of powder aerosolisation and may not addressall previously mentioned problems of prior art devices.

[0012] In addition, one particular disadvantage of the Inhale device isits large size. The Inhale system generates a substantially laminar flowof, e.g. powder. Thus, in order to achieve the necessarydeagglomeration, a large dose of high impact air must be delivered inorder to achieve the magnitude of impact required for deagglomeration ofthe powder. Thus, the Inhale system suffers from the disadvantage that,inter alia, is cumbersome and does not readily lend itself to a portabledelivery system.

[0013] International Patent application No. WO 01/87378 to Dura,describes a dry powder inhaler wherein a powder port extends into adispersion tube. A small burst of compressed gas is released into thedispersion tube and expands, the rapidly moving and expanding gasdisperses the powder and entrains the powder in the gas flow. However,the device suffers from the disadvantage that, inter alia,deagglomeration of the powder remains unsatisfactory.

[0014] U.S. Pat. No. 5,740,794—Inhale describes an inhalation apparatuswhich comprises, inter alia, a powder containing receptacle. A feed tubeis positioned so that an inlet end of the tube enters the receptacle anda high pressure gas stream is released which creates a ‘low pressureregion’ at the outlet end of the feed tube. Tis low pressure region actsto draw fluidisation air into the receptacle, to fluidise and extractthe powder through the feed tube and into the high velocity gas stream.

[0015] However, there is no disclosure that the powder will undergo acirculatory trajectory on its way to the mouthpiece. Indeed, thedisclosure, for example in FIG. 12 of Inhale describes a system whereinthe powder is evacuated from the receptacle through a ‘central’ feedtube, no substantial circulatory motion being introduced.

[0016] Furthermore, the description refers to an “undisrupted” flow pathfor the powder, which would lead one to conclude that a “feed tube”which is central rather, than one which is peripheral, is desirable.

[0017] International Patent Application No. WO 00/45878—Fraunhoferdescribes a device which utilises a vacuum aerosolisation of aliquid/powder. However, it is notable, particularly from FIG. 2, thatthe powder/liposome travels through the central conduit with compressedair circulating around the outside of the conduit.

[0018] Thus there has long been a need for a powder delivery systemwhich is capable of overcoming the aforementioned disadvantages.Attempts have been made to improve the respirable fraction of a powder(FPF) but these generally comprise the use of very low densityparticles. For example U.S. Pat. No. 6,254,854 describes the use ofparticles with a density of less than 0.4 g cm⁻³, whereas conventionalparticles in powders administered, e.g. by inhalation, may have adensity of about 0.8 to 1 g cm³.

[0019] Thus, there is clearly a need for the development of a devicesuitable for the delivery of particles of any density, which provideslow powder retention and provides a high respirable dose. For example,particles of conventional density, or low density particles ashereinbefore described, or even higher density particles.

[0020] We have now developed a powder delivery system which may comprisea number of high efficiency, controllable, elements and thereforeovercomes or mitigates the disadvantages of the prior art. In particularthe powder delivery system of the present invention overcomes theproblem of MDIs by separation of the propellant volatile fluid and thepowder. Furthermore, the powder delivery system of the inventionovercomes the problems associated with prior art DPI devices and, interalia, provides a greater efficiency of aerosolisation. It is thereforeespecially suited for use as a portable or hand held delivery device.

[0021] Thus according to a first feature of the invention we provide anair amplifying system comprising an amplify fluid jet provided with afluid inlet and a fluid outlet, the fluid outlet being linked to anoutlet nozzle via an amplifying passage, the amplifying passage alsobeing linked to a powder chamber, said chamber being adapted fornon-laminar powder flow, such that fluid travelling from the fluidoutlet of the jet draws extraneous air and aerosolised powder throughthe powder chamber so that the extraneous air and aerosolised powder mixwith the amplifying fluid in the amplifying passage and the amplifiedmixture exits through the outlet nozzle.

[0022] In particular, the ail amplifying system of the inventionutilises an amplified fluid, e.g. gas, stream to disperse a powder. Anunamplified gas stream can be created which is of sufficient velocity,for example by passing through an amplifying jet, so that, as it exitsthe jet and passes across an amplification passage, in the form of afirst opening of a contiguous powder chamber or conduit, the gas streamcreates a vacuum in the contiguous chamber or conduit.

[0023] The chamber or conduit can be provided with a powder reservoir ora powder metering member adjacent au inlet to the powder chamber, suchthat the vacuum created by the exit of the gas stream from theamplifying jet creates a vacuum in the powder chamber and an entrainmentair flow through the powder.

[0024] This entrainment air flow is sufficient to cause deagglomerationand/or entrainment and then subsequent aerosolisation of the powder. Oneeffect of the vacuum is to deagglomerate the powder without directimpingement of the gas stream on the powder. This may limit impaction ofpowder and hence retention of powder within the device which may be aproblem with some prior art devices. Moreover, the gas stream can alsobe adapted to be deflected against a solid surface, the effect being thetendency of the flow to become attached to or flow around the solidsurface. The exploitation of this effect, therefore enables a ‘shape’ tobe given to the existing gas stream. One advantage of the system of theinvention is that, inter alia, it provides a greater efficiency ofdeagglomeration and/or aerosolisation over prior art devices by thedirection of the entrained air.

[0025] We have especially found that by influencing the shape of the gasstream to have a substantially non-laminar motion provides animprovement in the deagglomeration of the powder reflected in asignificant improvement in respirable or fine particle fraction (FPF) ofthe delivered powder aerosol and a reduction in the powder retentionwithin the device. Furthermore, Computational Fluid Dynamics (CAD)studies indicate significantly improved fluid dynamics.

[0026] In a particular preferred embodiment of the invention the powderchamber is adapted such that the aerosolised powder is deliberatelysubjected to a non-laminar flow. Preferentially, the non-laminar flowmay be achieved by the use of an annular powder chamber. Thus, inparticular, the air amplification system of the invention is providedwith an annular powder chamber and an axial fluid jet.

[0027] Thus, in one embodiment of the invention the powder chamber maysubstantially form the body of the amplification system or becircumferential to the body of the device and the amplifying fluid jetmay be axial to the body. In this particular embodiment the powderchamber may be a thin annular chamber. Preferably, the thin annularchamber may be created by bringing together male and female portions.Therefore, the outlet end of the fluid jet may comprise, oralternatively, may be fitted to, a frusto conical male member which fitsinto an outer portion of the powder chamber, e.g. in the form of afemale member.

[0028] In this embodiment of the invention the separation between themale and female members may vary. Preferably, the separation between themale and female members which may be identified as the clearance may befrom 100 to 5000 μm, preferably from 500 to 2000 μm. Most preferably,the clearance may be about 1000 μm.

[0029] Thus, the diameter of the jet may be from 100 to 500 μm,preferably from 200 to 300 μm, most preferably 250 μm. The diameter ofthe nozzle may vary, but may be from 100 to 1500 μm, preferably from 400μm to 1200 μm especially from 400 μm to 600 μm, e.g. 500 μm.

[0030] In the air amplifying system of the invention the dimensions ofthe nozzle and jet may vary depending, inter alia, upon the nature ofthe powder to be delivered. However, importantly, the nozzle shouldpossess a greater diameter than that of the diameter of the jet. Thisparticular aspect of the invention is advantageous in that as the fluid,e.g. air, leaves the jet through the nozzle it expands creating a vacuumin the adjacent powder chamber. Thus, the ratio of the diameter of thejet to the diameter of the nozzle may vary, but may be in the range offrom 1:8 to 1:2, preferably 1:4 to 1:2 and especially 1:2. Furthermore,in the air amplifying system of the invention the shape of the nozzlemay be changed and/or multiple nozzles may be used to, inter alia,reduce oropharyngeal deposition. A particular advantage of the presentinvention is that, inter alia, the air amplifying system has the abilityto “slow” the aerosol. Conventionally known inhalers require the use of,for example, a spacer tube to achieve this. Thus, the air amplifyingsystem cam ‘slow’ the aerosol without the use of such a spacer tube.

[0031] The powder reservoir and/or metering member may be contiguouswith the powder chamber. Alternatively, the powder chamber may beconnected to the powder reservoir and/or metering member by one or moreconduits.

[0032] The air amplifying system of the invention may be useful in avariety of situations. However, it is especially useful whenincorporated in a powder delivery device.

[0033] Thus according to a second feature of the invention we provide apowder delivery device which comprises a delivery passage, a powderreservoir and/or a metering member adapted to present a measured dose ofpowder to the delivery passage characterised in that the powder deliverydevice is provided with an air amplification system as hereinbeforedescribed.

[0034] In a particularly preferred embodiment of the invention, the airamplifying system creates an entrained air flow through the powderreservoir and/or metering member. Thus, the powder reservoir and/ormetering member, may be positioned adjacent a powder inlet and the flowthrough the amplifying jet is sufficient to draw entrained air andpowder through the inlet. The reservoir and the metering member may beseparate, e.g. a bulk powder reservoir with a metering member.Alternatively the reservoir and metering member may comprise a singleitem, thus, for example, the device of the invention may be providedwith one or a plurality of prefilled metering members.

[0035] It should be understood that the basis of this aspect of thepresent invention is the creation of a pressure differential across orthrough the powder reservoir and/or metering member which enables thedeagglomeration of the powder to occur. Therefore, the creation of apressure differential may generally comprise the creation of a vacuum.It is especially preferred that the entrained air will flow through thepowder which is presented either direct from the reservoir or,preferentially from the metering member. Thus, preferably, the entrainedair inlet will be positioned adjacent to a first side of the reservoirand/or metering member and the vacuum is created adjacent a second,opposite side of the reservoir and/or metering member. In a furtherembodiment, a further inlet tube may be provided which is adapted tointroduce entrainment air, e.g. flushing air into the reservoir/meteringmember.

[0036] It is further preferred that the entrained air flow is sufficientto both deagglomerate and aerosolise the powder, although, ashereinbefore described, inter alia, improved deagglomeration can beachieved by the use of a non-laminar entrained air flow.

[0037] The air amplifying system of the invention may be used inconjunction with a variety of delivery devices. However, the powderdelivery system is especially suited for use in the delivery of apowdered medicament. Such a system may be used for the delivery of antype of powdered medicament, but the system finds particular utility inthe delivery of an inhaled medicament. Thus the system of the inventionmay be used as or in conjunction with an inhaler, e.g. a dry powderinhaler.

[0038] Thus according to a preferred aspect of the invention the powderdelivery device of the invention may be an inhaler. We especiallyprovide a, dry powder inhaler characterised in that it incorporates apowder delivery device as hereinbefore described.

[0039] In a further embodiment of the invention the amplification systemmay be provided with a plurality of nozzles and/or a plurality fluidjets. Such a plurality of nozzles and/or jets may increase the volume ofpowder which may be drawn the powder chamber. At the same time the totalvelocity of the fluid flowing through the jets and/or exiting throughthe nozzle. This is especially advantageous in the case of delivery of apowdered medicament, e.g. in an inhaler, since it enables a low velocityaerosolised powder cloud to be generated. In a yet further embodimentthe fluid jet may comprise a plurality of interlocking jets. In such acase each jet may, optionally, be provided with one or more powderinlets. Furthermore, the system may be arranged to provide the separate,sequential or simultaneous operation of the jets to enable the creationof an aerosolised powder which coincides with, for example, theinspiration of a patient.

[0040] When the vacuum means comprises a Venturi-type system ashereinbefore described the pressurised fluid may be any fluid movingsystem. The fluid may be a liquid, however, preferentially, the fluid isa gas, for example, compressed air or a gas/vapour generated from thevolatilisation of a volatile propellant, such as that delivered from apressurised canister. Alternatively, the fluid flow may be generated byan electric motor, e.g. a battery operated motor, or by a manuallyprimed piston, e.g. a hand pump.

[0041] When the vacuum means comprises the use of a volatilisedpropellant, any conventionally known pharmaceutically and/orenvironmentally acceptable propellants may be utilised. Such propellantsinclude, but are not limited to, non-CFC propellants, such as ahydrofluoroalkane (HFA). Any conventionally known HFA propellant may beused, including those disclosed in, for example, EP0372777, WO91/04011,WO91/11173, WO91/11495 and WO91/14422. However, the most preferred HFAis a fluoroalkane such as a fluoromethane or a fluoroethane or a mixtureof fluoroalkanes. Such fluoroalkanes include, but are not limited to,trichlorofluoromethane, dichlorodifluoromethane,1,2-dichlorotetrafluorethane, trichlorotrifluoroethane andchloropentafluoroethane. One HFA which may be mentioned is HFA 134(1,1,1,2-tetrafluoroethane) or HFA 227.

[0042] When the delivery device of the invention is utilised as or inconjunction with an inhaler, it is especially advantageous utilisationof entrained air not only deagglomerates the powder but also helps tofacilitate aerosolisation of the powder.

[0043] When the powder delivery device comprises an inhaler, it maycomprise a conventionally known inhaler with a system of the inventionattached thereto. An example of a conventional inhaler is a CLICKHALER(available from Innovata Biomed in the UK and described in EuropeanPatent application No. 0 539 469) which is provided with an inhalationpassage. The delivery device of the invention may optionally beattached, for example, at the outlet end of such an inhaler, to a spacerdevice.

[0044] In one embodiment, the metering member is adapted to transfermeasured doses of powder from the powder reservoir to the deliverypassage.

[0045] However, in an alternative embodiment, the powder may bepresented to the delivery passage in a closed form, wherein it is openedin the delivery passage. Thus, the metering member may be a capsule, inwhich case the device may optionally be provided with means for piercingor rupturing the capsule.

[0046] In a yet further and preferred embodiment the powder may bepresented to the delivery passage in an open form. Thus, for example,the metering member may be a spool carrying a powder, in which case thedevice may be provided with means for presenting the spool, in an openform into the delivery member.

[0047] Thus, the metering member may comprise a spool housed in a spoolcarrier. Such spools are generally described in the prior art. Anexample of such an inhaler system is a TECHNOHALER (available fromInnovata Biomed in the UK and described in European Patent ApplicationNo. 0 626 689). Each spool has a flange at each end which form a tightslidable fit within the body of the spool carrier. The space leftbetween the body of the spool and the spool carrier is filled with anappropriate powder. In an alternative embodiment the delivery device maybe provided with a spool chamber, for example, in the form tube adjacentthe delivery passage. In a preferred embodiment the spool chamber mayform a snug fit around the spool and may therefore replace the spoolcarrier. The spool chamber may therefore optionally be fitted with anactuator member which may comprise a push rod mechanism.

[0048] The delivery device of the invention is advantageous in that,inter alia, it may operate by the administration of a cloud of powder.The device provides a dry powder delivery system which is independent ofthe rate of inspiration of a patient, and without the need for a patientto inhale undesirable propellants.

[0049] Furthermore, the inhaler of the invention is especiallyadvantageous in that, inter alia, it may provide a significant increasein the respirable fraction of a delivered powder. As hereinbeforedescribed, it is a particular aspect of the inhaler of the presentinvention that the inhaler may not require the use of a spacer, butstill be able to “slow” the aerosol.

[0050] A variety of powders may be administered by using the inhaler ofthe invention. Such powders are generally drugs for the treatment ofasthma, chronic obstructive pulmonary disease and respiratoryinfections. Such powders include, but are not limited to B₂-agonists,e.g. fenoterol, formoterol, pirbuterol, reproterol, rimiterol,salbutamol, salmeterol and terbutaline; non-selective beta-stimulantssuch as isoprenaline; xanthine bronchodilators, e.g. theophylline,aminophylline and choline theophyllinate; anticholinergics, e.g.ipratropium bromide; mast cell stabilisers, e.g. sodium cromoglycate andketotifen; bronchial anti-inflammatory agents, e.g. nedocromil sodium;and steroids, e.g. beclomethasone dipropionate, fluticasone, budesonideand flunisolide; and combinations thereof.

[0051] It is within the scope of this invention for two or more powdersto be administered.

[0052] Specific combinations of powders which may be mentioned includecombinations of steroids, such as, beclomethasone dipropionate,fluticasone, budesonide and flunisolide; and combinations of toβ₂-agonists, such as, formoterol and salmeterol. It is also within thescope of this invention to include combinations of one or more of theaforementioned steroids with one or more of the aforementionedβ₂-agonists.

[0053] Further powders which may be mentioned include systemicallyactive materials, such as, proteinaceous compounds and/ormacromolecules, for example, hormones and mediators, such as insulin,human growth hormone, leuprolide and alpha interferon; growth factors,anticoagulants, immunomodulators, cytokines and nucleic acids.

[0054] It is within the scope of this invention to include combinationsof any of the aforementioned medicaments.

[0055] The particle size of the powder may be varied depending, interalia, on the type of aerosol being formed. In the case of a dry powdermedicament, the particle size of the powder, and the carrier, if one ispresent may be varied. The nature of the carrier may also be varied.Thus, the particle size of the powder may be substantially between 1 and100 μm. That is, at least 90% w/w of the powder should have a particlesize of between 1 and 100 μm. The preferred particle size may alsodepend upon the nature of the powder being delivered. Thus, for example,for the treatment of respiratory disorders a particle size of 4 to 8 μmmay be preferred, e.g. 6 μm.

[0056] However, for the delivery of systematically active powders asmaller particle size may be desirable, for example from 1 to 5 μm, e.g.2 μm.

[0057] In a dry powder formulation a variety of carriers may be used.Certain carriers may be mentioned, by way of example only, such assugars, e.g. dextran, mannitol and lactose, for example α-lactosemonohydrate. The particle size of the carrier may be across a widerange, between 0.1 and 500 μm, preferably between 1 and 200 μm.Alternatively, the carrier may itself comprise a mixture of fine andcoarse particles.

[0058] According to a further feature of the invention we provide amethod of administering a medicament which comprises the use of a powderdelivery device as hereinbefore described.

[0059] As previously mentioned the powder delivery device of theinvention is especially suited for use as a medicament delivery device,e.g. an inhaler. Therefore, we further provide a method of treatment ofa patient with a respiratory disorder which comprises the administrationof a powdered medicament using a device as hereinbefore described. In anespecially preferred embodiment the method comprises administration ofmedicament by inhalation.

[0060] In a preferred embodiment we provide a method of treatment of apatient with a systemic disorder which comprises the administration of amedicament using an inhaler as hereinbefore described.

[0061] The device of the invention is especially suited for theefficient delivery of macromolecules, such as insulin. Thus, accordingto a particular feature of the invention we provide a method of treatinginsulin dependent diabetes which comprises administration of aneffective amount of insulin using a device as hereinbefore described.

[0062] When the device of the invention is used for the delivery ofmacromolecules, such as insulin, it is important that they be providedin a moisture resistant system. Thus, according to the invention weprovide a device as hereinbefore described provided with a moistureresistant coating e.g. a paraxylylene coating.

[0063] The device of the invention is advantageous un that, inter alia,a significantly increased respirable fraction is achieved. Aconventional inhaler might be expected to deliver a respirable or fineparticle fraction of, for example, 20-40%. However, the delivery deviceof the invention is able to provide an FPF of in excess of 70%.

[0064] The respirable fraction of a powder, known as FPF is generally ameasurement of the percentage of a powder that reaches the lung of apatient as of function of the delivered dose. Respirable powderparticles are considered to be about 6 μm (aerodynamic diameter) or lessand therefore the FPF value of an aerosolised powder is a measure of thepercentage of particles with the desired respirable size. A deliverydevice with a high FPF value is therefore desirable. Conventionallyknown DPI's provide an FPF of about 20-30% w/w.

[0065] One measure of the efficiency of a delivery device is thedifference between the metered dose (MD) and the delivered dose (DD),conventionally this is known as the retention. Thus, a delivery devicewith low retention is desirable. Conventionally known DPI's provide apowder retention of approximately 10% w/w.

[0066] Conventionally know DPI's that provide a high FPF will provide arelatively high powder retention. Alternatively, those DPI's thatprovide a low powder retention may provide a relatively low FPF.

[0067] The delivery device of the invention is advantageous in that,inter alia, it provides a high APT and a low powder retention. Theachievement of a combined high FPF and low retention in a dry powderinhaler is novel per se.

[0068] Thus, according to a further aspect of the invention we provide apowder delivery device characterised in that the delivery deviceprovides a high FPF and low powder retention.

[0069] In a preferred aspect of the invention the delivery device of theinvention is a dry powder inhaler.

[0070] Thus we especially provide a delivery device as hereinbeforedescribed which comprises a substantially axial jet and a substantiallyannular deagglomeration chamber.

[0071] The dry powder inhaler may therefore provide an FPF of at least70% w/w. Preferably, the dry powder inhaler of the invention may providean FPF of at least 80% w/w, more preferably at least 90% w/w and mostpreferably at least 95% w/w. The dry powder inhaler of the invention mayprovide a powder retention of less than 10% w/w, preferably less than0.5% w/w and most preferably less than 2% w/w.

[0072] According to a further aspect of the invention we provide amethod of delivery of a powder with a high FPF and low powder retentionas hereinbefore described which comprises the use of a delivery devicecomprising an air amplifier.

[0073] According to a further aspect, we provide a method of treatmentof a patient suffering from a respiratory disorder which comprises thedelivery of a medicament powder comprising a high FPF and low powderretention.

[0074] The invention will now be described by way of example only andwith reference to the accompanying drawings in which:

[0075]FIG. 1a is a schematic cross-section of an air amplifying systemof the invention;

[0076]FIG. 1 is a perspective representation of a single chamber deviceof the invention

[0077]FIG. 2 is a perspective representation of a disassembled singlechamber device of the invention;

[0078]FIG. 3 is a cross-sectional representation of a single chamberdevice of the invention;

[0079]FIG. 4 is a perspective representation of a multi axial nozzledevice of the invention;

[0080]FIG. 5 is a perspective representation of a disassembled multiaxial nozzle device of the invention;

[0081]FIG. 6 is a cross-sectional representation of a multi axial deviceof the invention;

[0082]FIG. 7 is a perspective representation of a multi axial nozzledevice of the invention provided with a plurality of powder inlets;

[0083]FIG. 8 is a perspective representation of a disassembled multiaxial nozzle device of the invention provided with a plurality of powderinlets;

[0084]FIG. 9 is a cross-sectional view of a multi axial nozzle device ofthe invention provided with a plurality of powder inlets;

[0085]FIG. 11 is a cut-away perspective representation of a disassembledmultijet device of the invention;

[0086]FIG. 12 is a cross-sectional view of a multijet device of theinvention;

[0087]FIG. 13 is a perspective representation of a multijet device withindividually activatable powder inlets;

[0088]FIG. 14 is a cut-away perspective of a disassembled multijetdevice with individually activatable powder inlets; and

[0089]FIG. 15 is a cross-sectional representation of the device of FIG.14.

[0090]FIGS. 16a-c are cross-sectional schematic representation of thesystem of the invent, illustrating the sequence of operation of theinhaler;

[0091]FIG. 17 is a system of the invention;

[0092]FIG. 18a is a mathematical model of a static pressure contour plotthroughout the device of the invention;

[0093]FIG. 18b is a mathematical model of a static pressure contour plotthroughout a device of the prior art with main fluid flow from the sideand powder flow through the middle;

[0094]FIG. 19a is a mathematical model of a velocity magnitude contourplot throughout the device of the invention;

[0095]FIG. 19b is a mathematical model of a velocity magnitude contourplot throughout a device of the prior art with main fluid flow from theside and powder flow through the middle;

[0096]FIG. 20a is a mathematical model of the velocity of 5 μm particleswith a coefficient of restitution of 0.25, throughout the device of theinvention;

[0097]FIG. 20b is a mathematical model of the velocity of 5 μm particleswith a coefficient of restitution of 0.25, throughout a device of theprior art with main fluid flow from the side and powder flow through themiddle;

[0098]FIG. 21a is a mathematical model of the velocity of 5 μm particleswith a coefficient of restitution of 0.75, throughout the device of theinvention;

[0099]FIG. 21b is a mathematical model of the velocity of 5 μm particleswith a coefficient of restitution of 0.75, throughout a device of theprior art with main fluid flow from the side and powder flow through themiddle;

[0100]FIG. 22a is a schematic representation of the device of theinvention used in the experiment of Example 2; and

[0101]FIG. 22b is a schematic representation of the device of the priorart, with main fluid flow from the side and powder flow through the,middle, used in the experiment of Example 2.

[0102] Referring to FIG. 1a, an air amplifying system (1) comprises ahousing (2) and a fluid jet (3) provided with a fluid inlet (4) and afluid outlet (5). The fluid outlet (5) is linked to an outlet nozzle (6)via an amplifying passage (7). The amplifying passage is also linked toan annular powder flow chamber (8). The powder flow chamber (8) isadapted to provide a non-laminar flow path for the powder (not shown).The chamber (8) is also provided with an inlet (9).

[0103] In use, fluid travelling through the amplifying jet (3) drawsextraneous air through the powder chamber (8) aerosolising anddeaggromerating powder.

[0104] Referring to FIGS. 1 to 3, a powder delivery device (111)comprises a body portion (112), a powder inlet (113) and powder outlet(114). The body portion (112) comprises a male member (115) and a femalemember (116). The male member (115) is a substantially cylindricalmember provided with a frusto conical region (117) at one end (118). Thesecond end (119) is provided with an annular shoulder (120). Theshoulder (120) being provided with an annular recess (121) adapted toreceive an annular sealing ring (122). The male member (115) is providedwith an axial fluid flow chamber (123) provided with an inlet (124) andan outlet (125).

[0105] The female member (116) is adapted to fit over the male member(115). Thus the female member (116) presents a cavity (126) which isprovided with a frusto conical region (127) adapted to fit with thefrusto conical region (117) of the male member (115). The region of thecavity (126) dista to the frusto conical region (127) engages with theshoulder (120) of the male member (115). The end (128) of the femalemember (116) is also provided with an annular recess (129) to receive aportion of the annular sealing ring (122). Thus, an annular powderdispersion chamber (130) is created between the male member (115) andthe female member (116). The powder dispersion chamber (130) is providedwith an inlet (131) and an outlet (132), the outlet (132) beingcoincident with the outlet (125) of the fluid flow chamber (123) and theoutlet (114) of the female member (116).

[0106] In use, a gas, e.g. air or a volatile propellant passes along thefluid flow chamber (123), exiting at the outlet (125). At the junctionwith the powder dispersion chamber (130). The Venturi-type effect of thefluid flow creates a vacuum in the powder dispersion chamber (130)causing air to be drawn in at inlet (131).

[0107] Referring to FIGS. 4 to 6, a powder delivery device (211)comprises an annular body portion (212), and an end cap (213). The endcap (213) is provided with a central aperture (204) which is coincidentwith an aperture (215) created in the body portion (212). The end cap(213) is provided with an annular recess (214) adapted to receive anannular sealing ring (215). The end cap (213) is also provided with afrusto conical region (216) which surrounds the gas inlet aperture(214). The body portion (212) is also provided with a plurality ofannular jet rings (206). Each jet ring (206) is provided with a hollowfrusto conical portion (217) which surrounds a central jet aperture(218). Due to the hollow region (219) in a the frusto conical portion(217), the portion acts as a female member which fits over a male memberof the adjacent jet ring (206).

[0108] Each annular jet ring (206) is provided with a plurality ofspacers (220) to separate one ring from an adjacent ring. The space(221) between each ring (206) can therefore act as a powder inlet forpowder fed from cavity (222).

[0109] In use, a gas is fed through the inlet aperture (214) whichpasses through corresponding jet ring apertures (218). Thus creating ailincreased vacuum in cavity (222). Powder is fed into cavity (222) andexpressed through the jets and exits via aperture of the end jet (218d).

[0110] Referring to FIGS. 7 to 9, a powder delivery device (311) isanalogous to that illustrated in FIGS. 4 to 6. The body (312) of thedevice is provided with a plurality of apertures (314) which act aspowder inlets.

[0111] Referring to FIGS. 10 to 15, a powder delivery device (411)comprises a body portion (412), a powder inlet (413) ad a plurality ofpowder outlets (414). The body portion (412) comprises an annular wall(415) and end piece (416). The end piece (416) is provided with a gasinlet (407), an annular shoulder (417) and an annular recess (418)adapted to receive an annular sealing ring (419). The end piece (416) isprovided with a male member region (427) which engages with a jet holder(420). The jet holder (420) is provided with a plurality of jets (421)and is provided with a recess region (422) and surface (423) facing theend piece (416). The recess (422) presents a cavity (403) which isbeneath the jets (421). The jets (421) mate with powder outlets (414).Each of the jets comprises a frusto conical member (424) such that theshoulder of the cone (425) prevents the body portion (412) from restingagainst the jet holder (420) creating a powder delivery chamber (426).

[0112] In use, a gas, e.g. air or a volatile propellant passes throughthe inlet (407) into cavity (403) and through jets (421). TheVenturi-type effect of the fluid flow creates a vacuum in the powderdispersion chamber (426) causing powder to be drawn in at inlet (413).

[0113] Referring to FIGS. 16 and 17, a powder delivery system (51)comprises an axial fluid jet (502) with an out let (503) at one end(504). The jet (502) is surrounded by an annular powder deagglomerationchamber (505). The outlet (503) of the jet (502) meets thedeagglomeration chamber (505) and exits the system (501) at a nozzle(506). The deagglomeration chamber is comprised on a frusto conical malemember (507) and a corresponding female member (508). Thedeagglomeration chamber (505) is provided, at one side (509) with apowder delivery chamber (510).

[0114] The chamber (510) is provided with an inlet (511) and an outlet(512), at the end of au inlet conduit (513). The outlet (512) iscoincident with an inlet (514) into the deagglomeration chamber (505).The delivery chamber (510) is also provided with an air inlet (515)positioned at the end (516) of the delivery chamber (510) distal to theoutlet (512). In use, the inlet conduit (513) houses a metering spool(517) which carries a powdered medicament (518).

[0115] Referring to FIGS. 16b and 16 c, in use, the powder deliverysystem (501) is primed by inserting a spool (517) carrying powder (518)into the inlet conduit (513). The spool (517) is pushed to the end ofthe conduit (513) and into the delivery chamber (510). Compressed air isapplied (see arrow (519)) into the jet (502). Air flows through the jet(502) and leaves at the outlet (503). The exiting air creates a vacuumin the deagglomeration chamber (505) and causes suction in the powderdelivery chamber (510).

[0116] The air flow (shown by arrow 520) deagglomerates and subsequentlyaerosolises the powder (518) which passes out of the delivery chamber(510). Fine particles are capable of passing straight tough thedeagglomeration chamber (505) whilst larger particles collide with thewalls of the chamber (505) (and possibly with each other)) and aredeagglomerated to small respirable particles when they reach the nozzle(506).

[0117] Referring to FIG. 22; in FIG. 22a (Case 1) an air amplifier ofthe invention (221), comprises a central, axial jet (222), an annularpowder deagglomeration chamber (223) and a nozzle (224). The annulardeagglomeration chamber being provided with a powder inlet (225).

[0118] In FIG. 22b (Case 2) an air amplifier of the prior art (226),comprises a central, axial powder chamber (227), an annular jet chamber(228) and a nozzle (229). The annular jet chamber (227) being providedwith an air inlet (230).

EXAMPLE 1

[0119] CFD Examination of the Flow

[0120] Objectives of Study:

[0121] To generate a CFD model of the flow of air through twoconfigurations of the air amplifier of the invention.

[0122] To validate the air flow model by comparison with experimentaldata relating to prototype air amplifiers.

[0123] Geometry and Grid

[0124] A mesh was produced in ICEM-CFD using 235590 cells. Tetrahedralcells were used in the converging cone section of the geometry.Pentahedral cells were used in the straight pipe sections to reduce cellnumbers over a fully tetrahedral mesh.

[0125] Model Inputs—Continuous Phase

[0126] A constant absolute pressure equal to atmospheric was set at theoutflow boundaries (i.e., a gauge pressure of 0 Pa).

[0127] An ideal gas law was used for the fluid properties to allow forthe compressibility of air at the high Mach numbers induced.

[0128] The segregated solver was used, along with second-order upwinddiscretisation for all variables, and the SIMPLE velocity-pressurecoupling algorithm.

[0129] Standard k-ε turbulence model was used with viscous heating.

[0130] Boundary Conditions:

[0131] Case 1: Flow Through Centre, Drug from Side Region ValueTurbulent Intensity Length scale Middle inlet 3 Bar 5%  0.0001 m Sideinlet 1.735e−5kg/s 5%  0.0001 m Outlet 0 Pa 1% 0.00005 m

[0132] Case 2: Flow from Side, Drug Through Middle Region ValueTurbulent Intensity Length scale Middle inlet 1.735e−5kg/s 5%  0.0001 mSide inlet 3 Bar 5%  0.0001 m Outlet 0 Pa 1% 0.00005 m

[0133] Model Inputs—Discrete Phase

[0134] Density of drug particles was set at 800 kg m⁻³.

[0135] The total mass flow rate was set to 1.12×10⁻⁵ kg/s (equal to 2.8mg in 0.25 seconds, value supplied by IB).

[0136] The continuous phase and discrete phases were simulated both ascoupled and uncoupled.

[0137] The discrete phase boundary condition at wall surfaces was set to“reflect” with a coefficient of restitution of 0.25 and 0.75.

[0138] Turbulent interaction between the continuous and discrete phasewas modelled.

[0139] Initial particle speed was set to the average velocity magnitudeover the inflow boundary from which the particles were released.

[0140] Initial particle of 293K.

[0141] Particle size simulated 5 microns.

[0142] The drag law used for the simulations was the high-Mach-numberdrag law to account for the high velocities and large variations influid density seen in the simulations.

[0143] Number of particles tracked was 60 spaced evenly over the druginlet boundary.

RESULTS AND CONCLUSIONS

[0144]FIGS. 18a and 18 b show a static pressure contour plot from Case 1and Case 2 respectively.

[0145] A preliminary CFD study of the section pressure with the sideinlet blocked of to flow showed a negative static pressure of 529 mbar.Experimental results taken at IB give a suction pressure of 334 mbar onthe side inlet with a driving pressure of 3 bar on the central inlet.This corresponds sufficiently well to the CFD prediction to proceed withthe study of particle trajectories. In Case 1 the flow through thecentre induces a suction pressure of 122 mbar on the side inlet. Thus,as expected, the presence of the flow through the side inlet changes thepressure distribution.

[0146] Both the CFD and experimental results show that a positive 3 barpressure on the side inlet does not induce a suction pressure on thecentral inlet. Thus, in Case 2 a positive pressure on the central inletis needed to induce the correct mass flow rate (to allow comparisonbetween the two cases).

[0147]FIGS. 19a and 19 b show a velocity magnitude contour plot fromCase 1 and Case 2 respectively.

[0148] As expected, in Case 1 the highest velocity (>500 m/s) occurswhen the flow expand as it leaves the smallest diameter pipe through themiddle of the device and corresponds to the region where the air densityis at its lowest.

[0149] In Case 2 the highest velocity seen is smaller (>300 m/s) and isin the outlet section of the device. There is no point where the flow isaccelerated sufficiently for the density of the air to decrease belowits value at standard temperature and pressure, unlike Case 1. It is theexpansion of air in Case 1 that drives the larger velocities.

[0150]FIGS. 20a and 20 b show the trajectories of 5 micron particlesfrom Case 1 and Case 2 respectively when a coefficient of restitution of0.25 is used 5 micron particles have small enough inertia that they arestrongly effected by local air speeds.

[0151] In Case 1 particles are thrown out to the outside of theconverging vortex section and are then entrained into the boundarylayers of the exit flow. Turbulent eddies can knock the trajectoriesnearer into the middle of the flow but they tend to follow the outsideof the exiting flow.

[0152] In Case 2 the small inertia of the particles mean that theylargely follow the flow and do not collide with the wall surfaces. Theparticle trajectory simulations suggest that wall collisions are limitedto the converging section of the “(central) drug inlet” and the outletsection.

[0153]FIGS. 21a and 21 b show the trajectories of 5 micron particlesfrom Case 1 and Case 2 respectively when a coefficient of restitution of0.75 is used. The coefficient change has little effect on the overallresults from Case 2 because the particles do not often collide with thewalls. In Case 1 the coefficient change results in less momentum beinglost at each collision in the converging annulus section. Thus theparticles have enough momentum to remain in the rotating flow forlonger. They are drawn down into the converging section where eventuallythey are entrained into the main flow and through the outlet.

[0154] N.B. The image shows only 2 of the 12 particles tracked for theimage exiting the outlet. This is because the files produced when theparticles remain bouncing around the domain are very large, thereforethey are truncated for speed.

EXAMPLE 2

[0155] FPF aud FPD Measurements

[0156] Method

[0157] The objectives of the test were to assess and record theperformance of two main variants of the air amplifier system based onevaluation of the fine particle fraction (FPF) and the powder pick-up ordelivered dose (DD) and to access any blockage characteristics of thesystems, if any. The test work required the use of a steel amplifiersystem according to FIG. 22 manufactured at IB Tewkesbury to enableprecise and controlled setting of the geometries and orientations of thesystem. In addition plastic injection moulded components of the variantswere manufactured from the same facility and tested in the similar usinga similar protocol. Air amplifier variants were tested using a spraydried leucine preparation to represent the powder characteristics of atypical formulation for systemic drug delivery via the lung. FPF and DDwere determined gravimetrically using a modified glass twin impingerapparatus. Bach variant was tested using a two second pulse of air withfeed pressures of 5.7 and 3 bar. The two key amplifier system variantswere those which delivered powder through the “non linear, conical” sidepassage (the preferred embodiment denoted A (or Case 1 in the CFDstudy)) ad a variant B (or Case 2 in the CFD study) which deliveredpowder through the “linear central passage”. The results are illustratedin Table 1. TABLE 1 Nozzle Feed Offset Jet Dia. Dia. Press. AverageAverage FPD FPF Variant (mm) (μm) (μm) (bar) MID (mg) DD (mg) (mg) (%) A1.0 250 500 5.7 1.04 1.04 0.74 71.2% A 1.0 250 500 5.7 1.16 1.16 0.8270.7% B₅* 0.1 500 500 3.0 — — — — B₅* 0.1 500 500 5.5 — — — — B₆₅ 0.1500 650 3.0 1.04 1.04 0.38 36.5% B₆₅ 0.1 500 650 5.5 1.12 1.12 0.3934.8% B₇₅ 0.1 500 750 3.0 1.1 1.1  0.37 33.6% B₇₅ 0.1 500 750 5.5 1.141.14 0.43 37.7% B₈₅ 0.1 500 850 3.0 1.22 1.22 0.48 39.3% B₈₅ 0.1 500 8505.5 0.92 0.92 0.37 40.2%

1. An air amplifying system comprising an amplifying fluid jet providedwith a fluid inlet and a fluid outlet, the fluid outlet being linked toan outlet nozzle via an amplifying passage, the amplifying passage alsobeing linked to a powder chamber, said chamber being adapted fornon-laminar powder flow, such that fluid travelling from the fluidoutlet of the jet draws extraneous air and aerosolised powder throughthe powder chamber so that the extraneous air and aerosolised powder mixwith the amplifying fluid in the amplifying passage and the amplifiedmixture exits through the outlet nozzle characterised in that the powderchamber is an annular chamber which is adapted to provide non-laminarflow of the powder.
 2. An air amplifying system according to claim 1characterised in that the vacuum created by the exit of the gas streamfrom the amplifying jet creates a vacuum in the powder chamber and anentrainment air flow through a powder.
 3. An air amplifying systemaccording to claim 2 characterised in that the entrainment air flow issufficient to cause deagglomeration and/or entrainment and thensubsequent aerosolisation of the powder.
 4. (Cancelled)
 5. An airamplifying system according to claim 1 characterised in that systemcomprises an annular powder chamber and an axial fluid jet.
 6. An airamplifying system according to claim 5 characterised in that the powderchamber is substantially circumferential to the body of the amplifyingsystem and the fluid jet is axial to the body.
 7. An air amplifyingsystem according to claim 1 characterized in that the annular powderchamber comprises a male and a female portion.
 8. An air amplifyingsystem according to claim 7 characterised in that the outlet end of thefluid jet comprises a frusto conical male member which fits into afemale portion of the powder chamber.
 9. An air amplifying systemaccording to claim 7 characterised in that the separation between themale and female members (the clearance) is from 500 to 2000 μm.
 10. Anair amplifying system according to claim 9 characterised in that theclearance is about 1000 μm.
 11. An air amplifying system according toclaim 10 characterised in that the diameter of the jet is from 100 to500 μm.
 12. An air amplifying system according to claim 11 characterisedin that diameter of the jet is from 200 to 300 μm.
 13. An air amplifyingsystem according to claim 12 characterised in that diameter of the jetis about 250 μm.
 14. An air amplifying system according to claim 1characterised in that the diameter of the nozzle is from 100 μm to 1500μm.
 15. An air amplifying system according to claim 14 characterised inthat the diameter of the nozzle is from 400 m to 1200 μm.
 16. An airamplifying system according to claim 15 characterised in that thediameter of the nozzle is from 400 μm to 600 μm.
 17. An air amplifyingsystem according to claim 16 characterised in that the diameter of thenozzle is about 500 μm.
 18. An air amplifying system according to claim1 characterised in that the diameter of the nozzle is greater than thediameter of the jet.
 19. An air amplifying system according to claim 18characterised in that the ratio of the diameter of the jet to thediameter of the nozzle is from 1:8 to 1:2.
 20. An air amplifying systemaccording to claim 19 characterised in that the ratio of the diameter ofthe jet to the diameter of the nozzle is from 1:4 to 1:2.
 21. An airamplifying system according to claim 20 characterised in that the ratioof the diameter of the jet to the diameter of the nozzle is 1:2.
 22. Anair amplifying system according to claim 1 characterised in that thechamber is provided with a powder reservoir or a powder metering memberadjacent an inlet to the powder chamber.
 23. An air amplifying systemaccording to claim 22 characterised in that the powder reservoir and/ormetering member is contiguous with the powder chamber.
 24. An airamplifying system according to claim 22 characterised in that the powderchamber is connected to the powder reservoir and/or metering member byone or more conduits.
 25. An air amplifying system according to claim 1characterised in that the system comprises a plurality of nozzles. 26.An air amplifying system according to claim 1 characterised in that theand/or a plurality fluid jets.
 27. An air amplifying system according toclaim 26 characterised in that the plurality of jets comprises aplurality of interlocking jets.
 28. An air amplifying system accordingto claim 27 characterised in that each jet is provided with a powderinlet.
 29. A powder delivery device which comprises a delivery passage,a powder reservoir and/or a metering member adapted to present ameasured dose of powder to the delivery passage characterised in thatthe powder delivery device is provided with an air amplifying systemaccording to claim
 1. 30. A powder delivery device according to claim 29characterised in that the air amplifying system creates an entrained airflow through the powder reservoir and/or metering member.
 31. A powderdelivery device according to claim 30 characterised in that theentrained air flows through the powder which is presented either directfrom the reservoir or from the metering member.
 32. A powder deliverydevice according to claim 31 characterised in that the entrained airinlet is positioned adjacent to a first side of the reservoir and/ormetering member and a vacuum is created adjacent a second, opposite sideof the reservoir and/or metering member.
 33. A powder delivery deviceaccording to claim 30 characterised in that a further inlet tube isprovided which is adapted to introduce entrainment air into thereservoir/metering member.
 34. A powder delivery device according toclaim 30 characterised in that the entrained air flow is sufficient toboth deagglomerate and aerosolise the powder.
 35. A powder deliverydevice according to claim 29 characterised in that the device is aninhalation device.
 36. A powder delivery device according to claim 35characterised in that the inhalation device is a dry powder inhaler. 37.A powder delivery device according to claim 35 characterised in that theamplifying system is arranged to provide the separate, sequential orsimultaneous operation of the jet(s) to enable the creation of anaerosolised powder which coincides with the inspiration of a patient.38. A powder delivery device according to claim 29 characterised in thatthe fluid used in the fluid jet is a gas.
 39. A powder delivery deviceaccording to claim 38 characterised in that the gas is generated fromthe volatilisation of a volatile propellant.
 40. A powder deliverydevice according to claim 29 characterised in that the fluid flow isgenerated by an electric motor.
 41. A powder delivery device accordingto claim 29 characterised in that the fluid flow is generated by amanually primed piston.
 42. A powder delivery device according to claim39 characterised in that the propellant is a non-CFC propellant.
 43. Apowder delivery device according to claim 42 characterised in that thepropellant is a hydrofluoroalkane (HFA).
 44. A powder delivery deviceaccording to claim 43 characterised in that the HFA propellant isselected from those disclosed in EP0372777, WO91/04011, WO91/11173,WO91/11495 and WO91/14422.
 45. A powder delivery device according toclaim 43 characterised in that the propellant is a fluoroalkane.
 46. Apowder delivery device according to claim 45 characterised in that thefluoroalkane is a fluoromethane, a fluoroethane or a mixture offluoroalkanes.
 47. A powder delivery device according to claim 46characterised in that the fluoroalkane is selected from the grouptrichlorofluoromethane, dichlorodifluoromethane,1,2-dichlorotetrafluorethane, trichlorotrifluoroethane andchloropentafluoroethane.
 48. A powder delivery device according to claim47 characterised in that the fluoroalkane is HFA 134(1,1,1,2-tetrafluoroethane).
 49. A powder delivery device according toclaim 48 characterised in that the fluoroalkane is HFA
 227. 50. A powderdelivery device according to claim 36 characterised in that the inhaleris one described in European Patent application No. 0 539
 469. 51. Apowder delivery device according to claim 29 characterised in that themetering member comprises a powder housed in a spool and spool carrier.52. A powder delivery device according to claim 29 characterised in thatthe metering member is a capsule.
 53. A powder delivery device accordingto claims 51 or 52 characterised in that the device is provided withmeans for opening the metering member.
 54. A powder delivery deviceaccording to claim 51 characterised in that the spool carrier is anintegral part of the delivery device.
 55. A powder delivery deviceaccording to claim 29 characterised in that the powder is selected fromthe group of drugs for the treatment of asthma, COPD or respiratoryinfections such as β₂-agonists; fenoterol, formoterol, pirbuterol,reproterol, rimiterol, salbutarnol, salmeterol and terbutaline;non-selective beta-stimulants such as isoprenaline; xanthinebronchodilators; theophylline, aminophylline and choline theophyllinate;anticholinergics such as ipratropium bromide; mast cell stabilisers,such as sodium crornoglycate and ketotifen; bronchial anti-inflammatoryagents, such as nedocromil sodium; steroids, such as beclomethasonedipropionate, fluticasone, budesonide and flunisolide; and combinationsthereof.
 56. A powder delivery device according to claim 55characterised in that the combination of powders is selected fromsteroids, such as beclomethasone dipropionate, fluticasone, budesonideand flunisolide; and combinations of to β₂-agonists, such as, formoteroland salmeterol.
 57. A powder delivery device according to claim 29characterised in that the powder is systemically active.
 58. A powderdelivery device according to claim 57 characterised in that the powderis selected from a proteinaceous compounds and/or macromolecules, suchas hormones and mediators, such as insulin, human growth hormone,leuprolide and alpha interferon; growth factors, anticoagulants,immunomodulators, cytokines and nucleic acids.
 59. A powder deliverydevice according to claim 29 characterised in that the powder is acombination selected from a powder as defined by claim 55 and a powderas defined by claim
 56. 60. A powder delivery device characterised inthat the delivery device provides a high FPF and low powder retention.61. A powder delivery device according to claim 60 characterised in thatthe device is a dry powder inhaler.
 62. A powder delivery deviceaccording to claim 60 characterised in that the air amplifier comprisesa substantially axial jet and a substantially annular deagglomerationchamber.
 63. A powder delivery device according to claims 60 or 61characterised in that the device delivers an FPF of at least 70% w/w.64. A powder delivery device according to claim 63 characterised in thatthe device delivers an FPF of at least 80% w/w.
 65. A powder deliverydevice according to claim 664 characterised in that the device deliversan FPF of at least 90% w/w.
 66. A powder delivery device according toclaim 60 or 61 characterised in that the device provides a powderretention of less than 10% w/w.
 67. A powder delivery device accordingto claim 66 characterised in that the device provides a powder retentionof less than 5% w/w.
 68. A powder delivery device according to claim 67characterised in that the device provides a powder retention of lessthan 2% w/w.
 69. A method of administering a medicament which comprisesthe use of a powder delivery device according to claim
 29. 70. A methodof treatment of a patient with a respiratory disorder which comprisesthe administration of a medicament using a powder delivery deviceaccording to claim
 35. 71. A method of treatment of a patient with asystemic disorder which comprises the administration of a medicamentusing a powder delivery device according to claim
 29. 72. A method ofdelivering a powder wherein the powder has a high FPF and a low powderretention which comprises the use of a delivery device comprising an airamplifier.
 73. A method of delivering a powder according to claim 72characterised in that the air amplifier comprises a substantially axialjet and a substantially annular deagglomeration chamber.
 74. A method oftreatment of a patient suffering from a respiratory disorder whichcomprises the delivery of a medicament powder wherein the powder has ahigh FPF and low powder retention.
 75. An air amplifying system or apowder delivery device substantially as described with reference to theaccompanying drawings.